The transformations of .DELTA..sup.9 (.sup.11)-steroids to the corresponding bromohydrins (9.alpha.-bromo-11.beta.-hydroxy steroid) then to the corresponding 9.beta.,11.beta.-epoxy steroids and finally by reaction with hydrogen fluoride to the desired 9.alpha.-fluoro-11.beta.-hydroxy steroids are well known. Various agents have been used for the epoxidation reaction including strong bases such as methoxide, t-butoxide or sodium hydroxide in methanol (U.S. Pat. Nos. 2,838,493 and 3,725,392), potassium acetate in acetone (U.S. Pat. No. 3,980,778), and J. Am. Chem. Soc. 77, 4438 (1955), potassium fluoride in particular solvents (U.S. Pat. No. 3,255,185) and cyclic amidine bases such as DBU (U.S. Pat. No. 4,207,235).
The closure of the 9.alpha.-bromo-11.beta.-hydroxy bromohydrin to the corresponding 9.beta.,11.beta.-epoxide is a dehydrohalogenation reaction.
H. Oediger, et al. in Synthesis 591 (1972) compare the elimination of hydrogen chloride by various organic bases. Table 1 on p. 592 shows that cyclic and acyclic amines and acyclic amidines do not work in the dehydrohalogenation reaction nearly as well as DBN. Hence, it would be expected that acyclic amidines would not transform the 9.alpha.-bromo-11.beta.-hydroxy bromohydrin to the corresponding 9.beta.,11.beta.-epoxide nearly as well as does DBN or DBU.
D. H. R. Barton in J.C.S. Chem. Comm. 1136 (1981) reports the preparation of a number of guanidines which are strong organic bases. Barton did not report that these bases would be useful in a dehydrohalogenation reaction such as the transformation of a bromohydrin to the corresponding epoxide.
The present invention involves acyclic guanidines and amidines which surprisingly and unexpectedly efficiently effect the transformation of 9.alpha.-substituted-11.beta.-hydroxy steroids (I) to the corresponding 9.beta.,11.beta.-epoxides (II). The guanidines (III) and amidines (IV) are less expensive and easier to make than other known dehydrohalogenating agents such as DBU and DBN and do not cleave 21-acyloxy groups as to most other bases.